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Any physician may submit a question regarding a thyroid patient to  <ldegroot@earthlink.net>  or  ghennemann@hetnet.nl and one of our panel of expert thyroidologists will attempt to provide an answer as soon as possible by return Email. Physicians should provide adequate clinical information about the problem, and provide their name, office address, and telephone number. We will send an answer by Email to the address provided, and will publish the question and the response on this page. The name of the questioning physician WILL be published unless specific instruction not to do so is provided in the original Email. This service is available only to physicians.
Please note that Thyroidologists who hold opinions that differ from the advice we have offered are welcome to send in responses, and we will publish these comments. Commentators should kindly include name, office address, and Email address.

LIST OF TOPICS IN ORDER OF PRESENTATION BELOW---CLICK FOR HYPERLINk
QUESTIONS ANSWERED IN 2004-2005
 

BORDERLINE ELEVATED T3- / SUBCLINICAL HYPERTHYROIDISM?
QUESTION-,I would appreciate your input on the following case:> DD,a 9yrs and 7 month old white male, was first  referred to me 3 months ago for a goiter. He has ADD   and is on Concerta. He takes Claritin prn for  allergies.  He was recovering from an URTI, for which he had been
> on Amoxicillin. He denied sx of hypo or  hyperthyroidism except for 25 pound weight gain in 3
> months. There is no known thyroid disorder in the  family. > O/E his heigt and weight were at the 90% for his age.  PR 74/min. BP - 102/76.Thyroid was mildly enlarged. No  nodules, non tender. DTR 2+. No tremors. Rest of the   exam was normal. External genitalia -prepubertal. ?  Acne on chest, as diagnosed by dermatology.  His initial thyroid function tests (3 months prior to
 being seen by me), were as follows:
 TSH  - 1.47 (0.7 - 6.4); Total T3 - 2.58 (1.23 -
 2.110), Total T4  - 7.3 (5.3 - 11.6).
 I ordered the following tests:
 TSH - 0.64  (0.7-6.4), Free T4 - 1.14 ().9-1.6), Free
 T3 - 4.51 (2.3 - 4.20), T3U - 30.4% (27-37), TPO Ab
 18.8 (<35). Normal Dex. Sup.Test, FPG - 100, Normal  lipid panel.
 Thyroid USG - (R) - 4.1x1.2x1.3cms  (L) - 4.3x 1.3 x 1.4 cm. 0.4 cm cyst L lobe.
 Homogenous gland, otherwise.  Thyroid Uptake and scan was ordered to r/o a toxic
 adenoma vs SAT: 24% uptake at 24 hrs. Homogenous  tracer distribution, without hot or cold nodules.
 As he was clinally asymptomatic. I reassured mom that  he may ha subclinical hyperthyroidism. He was asked to  follow up in three months with TFT.  At 3 month follow up; his weight was up by 9 lbs,
 height increased by 1cm. Goiter noted.  His repeat blood work is as follows:
 TSH: 3.12. Free T4 - 1.03. Free T3: 4.84.
 What is his diagnosis?  Would you suggest any further  testing or Rx for this patient?
 I am not aware of increased T3 with Concerta or ADD.   I look forward to your comments and advice
 Radha Reddy  Chaparral Medical Group, CA

RESPONSE- With the normal TSH I do nOt think one can diagnose hyperthyroidism. It is not clear why his T3 is consistently slightly elevated. Perhaps he does have Hashimoto's thyroiditis despite the normal Ab test, which can occur in children. I am not aware of a condition with selective excess T4-T3 conversion. However with this situation watchful waiting seems in order. Leslie J De Groot, MD
 

HYPERTHYROIDISM AND AMENORRHEA
QUESTION-My patient is 27 G1P1 desirous of pregnancy who stopped DepoProvera 1/05 and continues to be amenorrheic. 

6/05 TSH = <0.03 and FT4=27.7

6/29/05 Scan = enlarged homogeneous gland c/w goiter

7/21/05 She received RAI

8/22/05 TSH=<0.03, FT4 = 0.80

She is not a patient patient and would like a specific idea of what to expect with regard to progress of thyroid function and, most specifically, when to expect resumption of menses and thereby return of fertility.  Can I be more specific than "usually a few weeks or months after RAI..."?  How often would you monitor her TFTs? Thank you for your service.J.R. Hoffman M.D.,Jasper, IN

RESPONSE-She is just days from being seriously hyperthyroid, and is probably rapidly on her way to hypothyroidism. I would follow closely- at least monthly- and institute therapy unless she recovers promptly. Perhaps her amenorrhea is related to hyperthyroidism, perhaps not. Have you checked PRL? If there is no other cause, she is healthy, and she reaches stable euthyroidism soon,  she should resume cycling in 2-4 months since she is only 27 and demonstrated prior fertility. L De Groot,MD.  24 Aaug 2005

GRAVES DISEASE AND INCIDENTAL THYROID CANCER

QUESTION-A 17 years old girl was totaly thyroidectomized for Graves disease and histologic examination revealed a focus of papillary carcinoma of 8 mm. Post thyroidectomy the TRAB is 10,5U/l (normal values < 11),  ATPO is >600 UI/ml( normal values <34),  and ATGL is 51,43 UI/ml (normal values < 115).

How do I best manage the patient? Shall I send her to radioiodine therapy or shall I just supress her TSH and check her thyroglobulin? Is the increased TRAB titer important in deciding therapy in this case?Any advice will be greately appreciated.Dr Cristina Dumitrescu,  Endocrinologist, Bucharest.

RESPONSE- The patient is probably cured. TRAb can stimulate growth of thyroid cancer. Follow up with TG will be difficult in view of the positive antibodies. Although one could simply follow on T4 with occasional US, personally I would prefer to ablate the residual (if any) . A negative scan would then be useful, and in time her TG antibodies should decline. You may still wish to do occasional ultrasounds.L De Groot,MD  24 Aug 2005

AGGRESSIVE MTC WITH POST-OP ELEVATED CT AND CEA (16 AUG 2005)
QUESTION-I hope you can help with this lady I saw recently.  She is a 59 y/o who was initially diagnosed with papillary thyroid ca after FNA of mass on right thyroid.  Surgical path surprisingly revealed medullary thyroid ca - initial pathology showed a dominant lesion in the right lobe 3.5 cm and a second 1.5 cm.  There was infiltration through the thyroid capsule into parathyroidal soft tissue and there was positive vascular lymphatic invasion.  2 of 2 LN in the central compartment were positive.  On the superior right, 3 of 3 nodes were positive; inferior right 7 of 7 nodes were positive and right lateral nodes 2 of 3 were positive.  The left lobe showed no disease.  One week after surgery - calcitonin was 64.9 ( no baseline was done as initial dx was papillary ca ) and CEA was 69.6.  Ret onc was negative.  24 urine met/cat were negative.  CT of neck, head, chest and abdomen were all normal.  

     Now,  2 and 1/2 months after initial labs were drawn and the radical neck surgery - her repeat calcitonin level is 132 pg/ml and CEA is 37.9  on exam I do not feel enlarged LN.  I have ordered an US of her neck and results of which are not back.  

     My questions are:  with almost doubling of calcitonin levels almost 3 months postsurgery ( 64 - 132 ) where else should I look for if the US of neck is negative?  Should I refer her for another neck exploration ?  Repeat CT of neck and chest even if the first one was done less than 3 months ago?  HOw significant is a calcitonin of 132 in terms of prognosis? Maria Mercado MD, Overland Park, KS 66213

RESPONSE-Information on what you mean by RET oncogene was negative would be of interest?  Exactly what was done? Any family history or exams or calcitonins?  The data (so far) suggests the tumor is a sporadic non-familial MTC,. And an aggressive type rather than the very slow moving type. I suppose residual  neck tumor on nodes on R (or L) are still an important possibility. I agree that it seems illogical to repeat the CAT scans in just 2 1/2 months. A PET scan might show something, but often with small lesions is not helpful. A bone scan is easy to do, but also probably unrewarding.   The elevated CT and CEA  + nodes and invasion  are ominous.

INFANT WITH GENETIC PROBLEM AND HYPOTHYROIDISM (16 Aug 2005)

Dear Sirs: First of all thank you very much for your help.

I have been consulted for a 3 year old boy who was born from un uneventfull pregnancy and delivery with an APGAR score of 1/8. TSH was informed as normal in neonatal screening and a TSH level of 6.54 mu/l was found  at two months of age. When he was 1 year old another test was done  because of developmental delay. TSH in that opportunity was 8.68 with a T4 of 11ug/dl. A pediatric endocrinologist repeated this  exam and TSH was about 2.55, T4 11, Free T4 1.16. So, no treatment was indicated.

At 1,6 years a new TSH of 7.98 was measured with FT4 of 1.24. He remains untreated until now  and comes to consultation with  a TSH of 5.43 T4 11.04 and a TRH/TSH test  of 9.77/ 61/51.Ft4 1.13

 He has a peculiar face. with some genetic stigmata ( hypertelorism. and strabismus . Ophthalmologic evaluation found a bilateral hypoplasia of the optic nerves and  impaired vision. His MRI is normal. He grew  in Percentile 10 of height and weight and 3 of Head circumference.

Do you consider that this boy suffers of  subclinical hypothyroidism?  Should he  receive treatment?

 Thank you again. Ana Chiesa, MD

A CHILD WITH NON-AUTOIMMUNE HYPERTHYROIDISM   (21 Jul 2005)
Dear Experts,  I was recently asked for a second opinion about a child now aged 10yrs 7 mos who has non-autoimmune hyperthyroidism first diagnosed at 3 yrs age following investigation for tachycardia.  Her initial FT4 was 77pmol/l and her TSH was <0.03mU/l.  As far as I am aware, FT3 was not formed.  All thyroid antibodies were and are negative.  The issue I was asked to discuss was whether radioactive
>>iodine was safe in children as definitive treatment for her condition, because the physicians primarily involved in her treatment would like to discontinue PTU.  That is not my question to you.

Salient features of this child include:
1) She has some subtle dysmorphism, namely a marfanoid body habitus with high arched palate, narrow face, arachnodactyly, mild thoracic kyphosis.
2) She  has mitral valve prolapse
3) she has hypoplastic cochleas on CT with low frequency hearing loss.
4) She is said to have some mild developmental delay.
5) she has a hyperfunctioning nodular goitre
6) She has been managed on PTU at a fairly low dose for several years.  This has resulted in FT4 levels in the low or low-normal range (around 6-12pmol/l) and FT3 levels in the high-normal to high range (similarly,around 6-12 pmol/l).  Her TSH has remained super-suppressed apart from a recent result (TSH 0.14mU/l, FT4 6.4pmol/l (low), FT3 6.3pmol/l (normal)).

   Her clinical findings however are mixed: significant growth failure over the past 4 yrs (97th to 25th percentlies), a history of persistent tachycardia investigated by her cardiologist and evident when I examined her, dry coarse hair, normal reflexes.  Her growth failure may be catch-down because her mid-parental height is on the 25th percentile.  A bone age obtained a couple of yrs ago was a months
>>advanced compared with her chronological age.

7) Reportedly, her mother and brother have normal thyroid function tests, her father has not been tested.  The paternal >grandmother developed hypothyroidism late in life.

      I am reasonably confident that she has a molecular defect responsible for her hyperthyroidism.  I think that this is most likely an activating mutation of the TSH receptor however the following things bother me:
1) Cochlea abnormalities and/or deafness have not been reported in association activating mutations of the TSH receptor (as far as I can tell) but have been reported in association with TRbeta mutations.  TRbeta mutations are also associated with a mixed picture of hyper and hypothyroid features, specifically the co-existance of persistent tachycardia and growth failure; however unless I am missing something, her TSH concentration excludes a TRbeta mutation.   Am I missing something?
2) MV prolapse would be consistent with an activating mutation of the TSH receptor.  Would local activation of TSH receptors in the heart explain the persistent tachycardia?  Are there any data on what happens to children (or indeed adults) with germline activating mutations of the TSH receptor post ablation with respect
to persistence of symptoms during thyroxine replacement therapy?  I have only found 1 case report that addresses long term follow up. From the point of view of her supposed hypothyroid signs, even if the plasma FT3 concentration is not a reflection of intracellular or nuclear T3, I cannot see why intracellular T3 would be low; therefore I do not understand the basis of her hypothyroid features, namely dry coarse hair and (if it is due to hypothyroidism) growth failure 

     I would appreciate any thoughts you may have on this child.  I have advised the parents that although radioactive iodine in appropriate doses would be safe, I think it would be advisable to understand better the underlying mechanism of her thyroid disease beforehand.  In the meantime, I have suggested trying to fully suppress thyroid function with a bigger dose of PTU and replacing her with thyroxine to mimic (more or less) what would happen post-ablation when she is on Thyroxine alone.  The family are very
>>willing to donate DNA for molecular analysis.  I therefore would also appreciate advice on who might be interested in looking at what.  I look forward to your response(s).
 Jan Walker MBBS FRACP,  Head, Endocrinology, Sydney Children's Hospital

 

RESPONSE-It is possible that she has an activating mutation in the TSH receptor (TSHR) but, without evidence of inheritance, which should be dominant, I cannot be as confident as you suggest. The absence of antibodies or other stigmata, such as ophthalmopathy and dermopathy, cannot exclude autoimmune thyroid disease (AITD) as the etiology of the thyrotoxicosis. She could be the product of a de-novo germline mutation. The only way to be sure is to sequence her TSHR, which is not difficult, in our day and age, to accomplish. I would be interested to know what you mean exactly by "hyperfunctioning nodular goiter"? Is the gland irregular but diffusely hyperfunctioning or is the increased radioiodide uptake confined to several nodules. Multiple somatic gain-of-function mutations have been reported, though not in children.
Resistance to thyroid hormone (RTH) due to a mutation in the thyroid hormone receptor (TR) beta gene is less likely for the reason you have stated below, namely suppressed TSH. This condition is also inherited as a dominant trait and, taking into account the prevalence of de-novo mutations, the chances are 85% that one of her parents should be also affected.
As far as I know TSHR is not expressed in the heart, and if it were, it is unclear to me how it will affect the heart by stimulating cAMP. Rather, the high thyroid hormone levels (mainly T3 in this case) is the likely reason for tachycardia. Incidentally, tissues that are more dependent of intracellular generation of T3 from T4, could be relatively hypothyroid. Human skin fibroblast have abundant type 2 5'-deiodinase.
Thus, the apparent T3-toxicosis may be the reason for some of the discrepant findings. Furthermore, neonatal thyrotoxicosis can produce a prolonged suppression of TSH (in man and in rat) presumably through its suppressive effect on the hypothalamus. Such individuals, and animals, can present prolonged post thyrotoxic central hypothyroidism.
Individuals with activating mutations are particularly resistant to antithyroid drugs and thyrotoxicosis has the tendency to recur after surgical ablation due to the persistent constitutive activation of the thyroid remnant. Thus, these patients are good candidates for radioiodide treatment, even at young age. Although this was not your question, I fully agree with your statement that confirmation of gain-of-function TSHR mutation before administering this form of treatment.
Regarding the somatic abnormalities, these may indicate that the genetic defect may be more extensive than just a point mutation in the TSHR. Have you done chromosomal analysis, either banding or by
the newer spectral karyotyping technique?  Samuel Refetoff, M.D.

CHOLESTASIS  FROM  MMI  (5 JUL 2005)

QUESTION- I am a pediatric endocrinologist and  I am seeing a girl of 10 years old otherwise healthy that presents to consultation with clinical and biochemical thyrotoxicosis. She began treatment with MMI 30 mg day and had an episode of cholestasis that remitted with withdrawal . As I did not see this episode myself and after a week she was normal( not jaundice) I reinstalled the treatment and  3 days latter I could see she developed this cholestasis again, that once more  disappeared after interrupting treatment. My question is if you have any experience on this adverse effect and if this child has any possibility of being treated with other antithyroid drug or if I should think of  I131.

 Thank you very much for your help   Ana Chiesa (achiesa@cedie.org.ar)

RESPONSE-Cholestatasis is a rare, reported side effect of treatment with methimazole.  The mechanism of action is different from the rare side effect of hepatotoxicity due to PTU and so, it is possible to cautiously switch the patient to PTU if you want.  Otherwise, I'd consider permanent thyroid ablation with either 131-I or surgery (if an experienced pediatric thyroid surgeon is available).  If you use RAI, I'd be sure to give an ablative dose.  

I'd refer you to the excellent recent review in the New England Journal of Medicine by Dr. David Cooper (2005;352:905-17)  Rosalind S. Brown, M.D.,  Rosalind.Brown@Children's.harvard.edu

RADIATION AND BREAST FEEDING(16 JUNE 2005)

QUESTION-I have a patient with papillary thyroid cancer with nodal metastasis. She was diagnosed when she was pregnant at 2 months. One month postpartum, she underwent total thyroidectomy, and is being evaluted for radioblation with suppressive therapy. She is currently breast feeding, and intends to breast feed her now 2 months old child. How soon after radioablation, she can restart breast feeding her baby, if at all? Will appreciate your reply.

Hiralal Maheshwari, MD, PhD, Crystal Lake, IL

RESPONSE-A possibility of course is to suppress TSH now and treat with 131I after breastfeeding has been discontinued. This is what I would prefer, as any contamination of the newborn with 131I should be avoided, which means a difficult situation for handling the child by the mother anyway for several  weeks after the treatment. To my opinion no harm is done to wait with 131I for a few months, provided that TSH is suppressed Georg Hennemann, MD, PhD, FRCP, FRCPE

NEONATE WITH POSSIBLE HYPOTHYROIDISM (16 JUNE 2005)

QUESTION-2 month old baby,male, was born full term, birth weight 3.2kg. No neonatal complications. No hipoglicemia, jaundice or micropenis. Normal newborn screening (Normal TSH and Free T4).

Maternal data: no medications during pregnancy or breastfeeding, no problems during pregnancy. Normal Thyroid function test.No hoarse cry, facial puffiness, umbilical hernia, hypotonia, mottling, cold hands and feet or lethargy. Active baby. No dysmorphisms.

During pediatric evaluation: protrusion of tongue and hepatomegaly (3cm) was noted so TFT was ordered at 2 months. Results Free T4 0.94 (normal value 1.0 - 2.0); TSH 1.0; normal T3 repeated twice in a good laboratory.rT3 and TBG ordered + new TFT in another lab (on the way). 

HD: Euthyroid sickness? due to ???? (no aparent cause),  2o or 3o hypothyroidism?, TBG deficiency?

Should we treat if new FT4 is low?  Is it crucial to check GH, LH, FSH, PRL, cortisol in the abscence of micropenis and hypoglycemia? Should we perform an MRI?  Does protrusion of tongue occur in 2o or 3o hypothyroidism as well? Thanks in advance for your help. Clarissa Pedreira

I would be concerned about either TBG deficiency or hypopituitarism in the baby.  It is unusual to see secondary (or tertiary) hypothyroidism in the absence of growth hormone deficiency as you are aware. I don't think it is likely to be sick euthyroid syndrome if the baby is not sick. 

Thyroid patient with asthma, allergy to carbimazole, ? allery to PTU

 QUESTION-A female patient around 40 yrs old, developed thyroid toxic symptoms, her free T4 is around 50. She was given CMZ but developed urticaria, she was prescribed the anti-allergy med with PTU, but she developed bronchospasm the next day. Both meds were stopped now.
1. should PTU be tried? is the allergy due to the residual effect of the CMZ
2. if PTU should not be used, how can we make the patient euthyroid before she can undergo RAI or surgery
3. Should RAI or surgery be preferred? Thank you very much. Dr. JL Paul

RESPONSE-suggest to administer propranol, dosage: 4 times 40 mg per day and treat with 131I. If she can not tolerate propranolol and the cause of her thyrotoxicosis is Graves’ disease, you can administer prednisone. Georg Hennemann, MD

RAI TREATMENT AFTER LUGOL’S IODINE 

QUESTION-I have a young woman who recently presented with thyroid crisis due to graves' disease. She was successfully managed with beta blockade, propylthiouracil, dexamethasone and 10 days of lugol's iodine. She is now controlled on thionamide alone. I would be grateful for your advice as to how long to wait before administering radioiodine, given that she has received lugols iodine. Would a tracer uptake be of benefit?

Many thanks, Hamish Courtney, Royal Victoria Hospital, Belfast (17 May 2005)

RESPONSE- Lugol's iodine is rapidly cleared from the body, especially in a thyrotoxic individual. Probably 2-3 days is enough, but I think you can be confident that after a week the RAIU will be back near the original level. On the other hand, I think you always would want to do an RAIU prior to treatment, anyway. Best regards,  L De Groot,MD

LIVER FAILURE AND SEVERE  THYROTOXICOSIS

QUESTION-An 18 yo AA Male with Graves disease was transferred to our hospital for liver transplant b/o acute liver failure while taking PTU. This has been d/c five days before the admission although low compliance was suspected. The TFT were still reflecting a suppressed TSH, high FT4 and FT3. Clinically the pt was thyrotoxic with sinus tachycardia and propanolol doses were increased. Corticosteroids were also started. While waiting for the liver the pt developed hemodynamic instability with supraventricular arrhythmias, hypotension and AMS. He required fluids, IV betablockade. No fever was documented. However, thyroid storm was considered and after correcting the coagulation, the pt was taken to the OR for total thyroidectomy. This went uneventful and the pt became more stable within 12 hours after surgery. 24 hours after  the pt underwent liver transplant. Two days after the thyroidectomy FT4 and FT3 levels were low. Albumin remained low for approx 8 days and slowly increased after that. LT4 was supplemented since POP day 2 after thyroidectomy, requiring 250 ugr/day to maintain FT4 within a normal range.

I would like to read your opinion about PTU liver toxicity, the management of thyroid storm in a case like this, and the use of FT4 measurements to guide the LT4 supplementation. Thanks. JM

RESPONSE- I will respond, but I note that I have never managed a case such as yours. Perhaps others will offer opinions as well. Your case seems special, difficult,  and interesting enough to be reported.

     Not knowing all of the facts, it does not seem illogical that a reaction to PTU caused the liver failure.  That is a well recorded problem. The approach you took is used frequently in managing patients with amiodarone induced thyrotoxicity. Possibly other agents such iodide, iopanoic acid ( in the presence of liver failure??) and amiodarone could have controlled the hyperthyroidism, but the method you used does, and did, work. I think I would have chosen freeT3 as the hormone assay to follow, since it probably represents more exactly the active hormone, whereas freeT4 might not be representative in a patient with presumed difficulty in deiodination. Why did the patient require a large amount ot T4 to maintain a normal freeT4 level? Possibly medication interfered with absorption. Possibly the assay is faulty in such a complicated condition. Possibly the patient's metabolism was still "hyperthyroid", and degraded T4 more rapidly at that point in the course than would have occurred in a euthyroid person. Best regards,  L De Groot,MD

 POSITIVE I-131 SCAN POST THERAPEUTIC I-131
QUESTION-The patient is a hearty 85yo gentleman who presented with a right neck mass,
subsequently diagnosed as metastatic papillary thyroid CA. The patient underwent total thyroidectomy with right modified radical neck dissection.  He had Hashimoto's thyroiditis with Hurthle cell changes and a focal hyperplastic nodule.  No primary CA found in the thyroid.  He had 6/16 nodes positive for metastatic papillary CA. He was treated with 156 mCi  I 131 subsequently.
A whole body I 131 scan done 2 weeks later revealed 3 areas of focal uptake in the contralateral neck suggestive of nodes, one at angle of mandible and two near the sternal notch.  He has no palpable
disease. Thyroglobulin- 1.2, TSH- 96.8  ,Thyroglobulin antibody- positive.
Can I 131 treatment be repeated or does this patient require a contralateral neck dissection?
Clifford Gelman, MD Melbourne, FL
RESPONSE-In the first place, the Tg blood value is probably of no use because Tg
auto-antibodies do interfere with the tests for Tg. If this patient would be below his seventies and healthy I would probably prefer neck dissection at the left side probably by the technique of node picking rather than a modified radical one. However as the growth rate of papillary cancer is very slow and considering the age of the patient, you may consider a further treatment with 131I and follow-up of the neck with US. By the way, are the found locations on 131-I scanning showing nodes on US? Is there US evidence for enlarged nodes that are not showing on 131I scanning? If there is full confirmation of findings between these techniques I would prefer 131-I treatment with US follow-up. However if there are "US positive nodes' but 131-I negative, I would rather consider surgery. Kind regards,  Georg Hennemann

 MINIMALLY INVASIVE FOLLICULAR CARCINOMA
QUESTION-I am still confused on the staging and management of a minimally invasive follicular carcinoma. As an example, I have a patient who is 35 years old  and had a 3.7cm minimally invasive follicular carcinoma resected with a  total thyroidectomy. The remainder of the gland showed only thyroiditis.  There was no vascular invasion noted.  This patient went on to receive remnant ablation and now has a  thyroglobulin level of <0.3 and a negative thyroglobulin antibody. A  follow-up scan was negative.
 My question is was this all necessary? Would you stage this as a T2N0M0  follicular carcinoma, or is different staging terminology used for  minimally invasive follicular ca. Also, would you have gone on to I131  ablation or is this not necessary and would you alter your long term  follow-up in this patient from that normally given to patients who have  T2M0N0 papillary or follicular carcinomas.  Thanks for your help,  Karen Kartun, M.D.
RESPONSE-There certainly is growing evidence that such minimally invasive tumors without vascular invasion behave in a very benign manner.  However, I remain cautious.  A 3.7 minimally invasive CA is still a danger, and the size is a significant factor. I believe I would follow her as a "regular" cancer patient at this stage.  She is apparently cured. Thus you probably will follow with TGs if you can (but what about her antibodies???), do periodic neck US, and I personally would do another scan in 2-3 years, and then reconsider the need for further scans. L De Groot,MD

 POSSIBLE RESISTANCE TO THYROID HORMONE

Dear Doctors:   A 3 9/12 year old boy was referred to us because of elevated T3, T4 and positive microsomal antibodies.   He has a history of developmental delay and hyperactive behavior.

9/2/04:

T4 = 14.3 (5-12.5)

free T4 = 1.79 (.77-2.02)

T3 = 353 (75-250)

TSH = 1.26 (.4-8.1)

antithyroglobulin ab (<20)

antimicrosomal AB = 131

  After phone consultation, the following labs were obtained on 11/23/04:

T4 = 9.3 (5.5-12.8)

free T4(dialysis) = 1.1 (.8-2.2)

T3=286 (75-250)

TSI = 92% (adult N<125%)

  He was seen at our clinic on 11/30.  Behavior was remarkably hyperactive but parents felt that this was typical and did not represent a recent change.  He had no history of change in his appetite, weight loss, polydipsia, polyuria or diarrhea.  He typically has had some difficulties sleeping through the night.  On exam, wt. was at the 90-95th %ile and ht. was at the 50-75th%ile.  BP could not be obtained but heart rate was normal after having the child sit for a few minutes.  He had no exophthalmos or goiter and the remainder of his exam was unremarkable.  PTU 45mg tid was started (7.5 mg/kg).  Inderal 5 mg tid was also recommended. On 1/7/05, labs were repeated:

free T4 = 1.6

T4 = 11.8

TSH = .68

T3 = 305

Mother reported no improvement in behavior at home or in school.  On 2/3/05, PTU was discontinues when the child developed a pruritic rash.  Tapazole 3 mg tid (.47mg/kg/day) was started a few days later but he developed an urticarial rash and this was discontinued after a few days.  The child was retested a few weeks later:

free T4 = 2.42. (.77-2.02)

T3 = 441 (75-250)

TSH = 1.53 (.4-8.1)

    I am not sure why his TSH has increased as T3 has increased.  Do you think that thyroid hormone resistance is a possibility even though he was positive for microsomal antibodies?  I have increased his inderal to 10 mg tid but I have not restarted antithyroid meds?  What do you suggest?   Thanks.  Lou Ann Gartner, M.D.  Buffalo, NY

RESPONSE- Dear Dr. Gartner:This is certainly a puzzling case.  I do not think that your patient is hyperthyroid both because of the normal TSH, the absence of goiter and the fact that he is at the 90th-95th %ile for weight. Also, in my experience, commercial TSI assays are insensitive and unreliable.  To R/O Graves' disease, I would therefore check TSH receptor Abs by binding assay (called either "TBII" or "TRAbs", depending on the lab).  Both Quest and Exotrix have reliable assays but any other commercial lab using the Kronus assay should also be able to do the assay. I suppose that the child could also have a TSH-secreting tumor (highly unlikely, to the extent that it is probably reportable at this age) so you could add a beta subunit. 

We certainly see mild thyrotoxicosis associated with Hashimoto's not infrequently in children, but Hashimoto's is sufficiently common that he may have the disease but it is asymptomatic and not related to the symptomatology.  Alternately, he could be making  Abs to T4 and T3, accounting for the high levels of these hormones in his serum. If you're stuck, and need to assess whether or not he is hyperthyroid, you could always do an 123-I uptake. 

That leaves you with TBG excess or thyroid hormone resistance.  Again, the absence of goiter, and the absence of failure to thrive make the latter dx less likely but not impossible. To R/O the former I would check TBG.I would hold off on treatment for the moment. I hope this is helpful to you.  I would be most interested in learning what you find. Rosalind S. Brown, M.D.

NB- The T3 suppression test for DDX of GRTH is described in Thyroidmanager, Chapter 16D. LDeG

PREPARATION FOR TREATMENT OF A TOXIC ADENOMA

QUESTION-I am wondering what is the proper way to prepare a  patient with toxic adenoma prior to rai. How long and  how much t4 do we give?  How about those patients who  are clinically and biochemically toxic?  Thanks so much Doctor for your generosity. L. W.Bilar, MD

RESPONSE-Usually in patients with a single toxic adenoma the rest of the thyroid is quite suppressed, so that there is little or no RAIU. In this situation the nodule can be treated, with only modest radiation to the rest of the gland, and typically with no preparation other than the RAIU and scan. If the patient is highly toxic, certainly pre-treatment with antithyroid drugs is possible, but rarely needed. Does this answer your questions?  L De Groot,MD

DIAGNOSIS AND TREATMENT OF NTIS  (1 March 2005)

QUESTION-I am an intensivist and I'm very confused about the literature about NTSI or "euthyroid sick syndrome".  As we now are used to use some kind of endocrine replacement therapy (fe. hydrocortisone, vasopressine) on a routine basis, we are currently reevaluating our approach to the NTSI. I read with great interest your article in J Endocrinol Invest 2003. One problem for me (as a non-endocrinologist): most of the literature discusses total T4 and T3 levels, but today we recieve from our laboratory results of FREE-T3- and T4-levels (chemilumineszenz-method). Is it possible with the free hormone levels to better evaluate, if there is a (chemical) hypothyroidism; or are there still a lot of analytic interferences that make the interpreation of the laboratory results difficult  ?

- what will be the usual pictures of FREE-T3/T4 in NTSI ?

- Could you recommend levels of free-T4 or T3, below that you would start replacemant therapy?

In our small experience, we have seen two groups of ICU-patients

a) isolated low free-T3 levels and normal TSH

b) low free-T3, +/- low freeT4, in combination with low TSH

 -What is your recommendation for a practical approach in ICU:

 -- replacement therapy only if free-T4 is under a certain limit?

 -- how would a low TSH influence your approach?

I thank you very much for helping us! rolf.ensner@ksa.ch <mailto:rolf.ensner@ksa.ch>

RESPONSE- PLEASE NOTE THAT I COME FROM A PARTICULAR POINT OF VIEW, BELIEVING THAT THESE PATIENTS HAVE A DEFICIENT SUPPLY OF THYROID HORMONE, WILL PROBABLY  BENEFIT FROM REPLACEMENT, AND THAT THERE IS  NO PROVEN DANGER IN TREATMENT.

The hallmark if NTIS is observation of a low T4, best estimated by a method that is believed to provide, or correlate with, free T4, in the setting of severe illness. Usually TSH is normal or low (rarely elevated), and T3  or free T3 is usually even more dramatically suppressed. Since low T3 alone has not been shown to correlate with bad outcome, I think one depends on a low free T4 as the test. In my mind any free T4 level clearly below normal in this setting brings up possible treatment, more urgently as the T4 becomes lower. The TSH level is more of a guide to causation, than to therapy. People talk about confusion with the low TSH of hyperthyroidism, but that is, in this setting, usually a rather bizarre consideration. We have given patients 30 ug T3 bid, and started 100ug T4, and followed blood levels closely. Obviously T3 is the required drug, if any, and T4 will only be supplemental as recovery proceeds. Unfortunately proof that this approach is correct is not available. Best regards,  L De Groot, MD

NODULES AFTER RAI THERAPY OF TMNG
Question-I believe RAI is the better option for toxic multinodular goiter. Can you comment on situations when
1) nodules become bigger year(s) post RAI, or minimal change if at all?
2) growth of new nodules post RAI. These patients are already on replacement doses of Lt4 for hypothyroidim(post ablation).I wonder if the kind of nodules affect treatment outcome? Does RAI affect solid nodules ,complex, or cystic nodules differently. Thanks very much for your sharing your expertise. Lynn Bilar,MD
RESPONSE- 1) The 131I scan of patients with MNG almost invariably shows a mixed picture of hot, low-uptake and even cold area’s. These cold area’s often, but not always, begin to show uptake after the other nodules have disappeared or at least shrunken by previous dose(s) of 131I. In other words if patients still have remaining or even growing nodules after 131I treatment, it means either that insufficient attention has been given to the possibility that cold nodules may start to take–up 131I after irradication of initially active nodules, or that nodules remain cold indicating structurally absence of uptake capacity. Then surgical treatment is only necessary when serious compressive complaints remain.
2) RAI only affects nodules that show uptake capacity for 131I. Most non-malignant solid or mixed nodules do, but the latter to a lesser extent. A pure cystic nodule, does not. Georg Hennemann, MD
Note added- Nodules growing after RAI treatment of TMNG must raise the question of malignancy, and deserve evaluation from that point of view. L De Groot,MD

• h41+ female, H ypothyroid since birth [uncertain of any presence of gland]
• medicated from 18mths
• oroxine medication monitored every few months. blood pathology indicating appropriate dose.
• dose for many years: 400mg daily.
• no notable deformities, other than stunted thumbs.
• patient treated for depression over past 12 months with cipramil 20-40mg. unsuccessful.
• recent agitation, anxiety, and depression led to hospitalisation;
• recently additional: feeling hot all the time; shakes internal and to some degree externally; worsening of agitation, anxiety and depression..
• blood tests reveal: free T4 @ 33.6H [normal upper limit of 19]; free T3 @ 7.5H [normal upper limit of 6.2]; TSH @ <0.01 [normal lower limit of 0.3]
• dose dropped to 300mg 3 days ago
• the concerns are a) could these extraordinary thyroid levels be contributing to the patient's crises; b) is there any permanent damage possible; and c) does the pathology suggest another condition or complication?
  thanking you in advance..Have a happi day ,
  Dr. Sifu Crockett ,HAPPI Foundation Ltd , www.happi.org.au
  RESPONSE--I do not connect stunted thumbs and congenital hypothyroidism, but maybe another reader can help. Regarding the blood hormone levels, certainly it seems that the patient has been under excessive thyroid hormone dosage, and needs to be reduced gradually to a level that keeps the TSH preferrably around 1-1.5, and the freeT4 in the high normal range. It probably will take many months for the pituitary to return to normal as you lower the dose. Regarding the future, I guess you wait and see. If the patient was untreated for 18 months after birth, that suggests a major developmental problem unless there was in fact significant endogenous thyroid hormone production at that time.  L De Groot,MD

THYROID HORMONE RESISTANCE vs. TSH-OMA ?
QUESTION- I wonder if I might get an opinion on what you would do next: 74 year old male had routine physical exam and labs done by his primary care physician in May. As part of laboratory panel a TSH and free T4 were done. The TSH was 1.64 (0.4-4.0) and the free T4 was 2.03 (0.68-1.76). These were repeated 7/8/04. TSH was 1.77, free T4 was 1.98 and T3 was 149(58-184). Patient then sent to endocrinology for evaluation. Per history he has been well and specifically denied any symptoms suggestive of hyperthyroidism. He has a daughter with a history of hypothyroidism. On examination his pulse was 68, EOMI, no lid lag, visual fields were intact to confrontation, thyroid was without goiter, nodules or bruits, no hyperreflexia or tremor was present. Labs were repeated 7/29/04 with TSH 1.60 (0.4-4.0), free T4 2.24 (0.68-1.76) and T3 134 (58-184), alpha subunit was 2.2ng/ml (normal < 1.0).
Thyroid hormone resistance syndrome vs TSH secreting adenoma vs other?? What would be recommended as the next step. T3 suppresion test? Get TFTs on family members? MRI?
K K, M.D. Fontana, CA 92335
RESPONSE- Dear Dr. K,
Thank you for your recent email. Dr. DeGroot has asked me to respond. The patient you describe appears to have elevated free T4 with normal TSH and normal T3 levels. The absence of an elevated TSH makes the diagnosis of RTH or TSHoma unlikely, but does not completely rule it out. It is possible that there is a binding protein abnormality or an antibody that is interfering with the free T4 assay used (or conversely there is something interfering with the TSH measurement). Given the elevated alpha subunit at this point I would agree that an MRI of the pituitary should be done. Your suggestion to get blood tests on other family members is a reasonable approach. If you and the family are interested we can evaluate the thyroid function along with binding proteins in our laboratory at the University of Chicago. While there would be no charge for the blood tests, the family members would be responsible for the expenses of phlebotomy and shipping of the blood. I have attached instructions for shipping as well as a consent form that should be signed by all the subjects. We should obtain blood from the propositus as well as his children and their spouses for starters. If other family members have a similar thyroid phenotype genetic testing may then be performed.
Roy E. Weiss, MD, PhD, FACP   rweiss@medicine.bsd.uchicago.edu

CHROIC URTICARIA, THYROXINE TREATMENT, THYROID CANCER

QUESTION-I ask to you to help me for curing this patient. She is 48 years old women, in 1996 diagnized that she have papillary carcinoma of thyroid gland, and then she did total thyroidectomy operation in same year outside Iraq. And postoperatively she took radioactive iodine. And after 6 monthes she did scaning , and from scanning it appear that she not need radioiodine therapy , and also after 6 monthes she also did another scanning also it appear that she not need radioiodine therapy, and after1 year she also did another scanning also it appear that she not need radioiodine therapy, and after 3 tears also she also did scanning it appear that she not need to take radioiodine therapy.(all of the scanning she did it outside of Iraq), after these scanning doctors outside Iraq decided that she is not needing to do any more scanning.She is from the date of her surgery of (total thyroidectomy)she is on thyroxine(T4)(0.1 mg)therapy. She is taking 2 tablets a day at morning, now her TSH is 0.05 UIU/ml.
Since 2 years she is suffering from a sever itching during night but also some time this itching occur during the day, with vaginal itching, the size of the wheals is 2 cm or less in diameter. Nearly she have this itching every night. I prescribed for her to take and she taken allermine, loratidine, betametazoneLA ampule for three weeks but there was no benefit. But when she apply Calamine lotion she is for a while feeling better. And I advised her to avoid some food like egg, onion, melon, potato, and nuts, and to be away from some types of flowers and clothes but also there was no benefit. I do not know how to solve her itching problem, to make her comfortable. WHAT CAN WE DO FOR HER TO SOLVE HER ITCHING PROBLEM? NOTES: We can not change the dose of thyroxine(T4) that she is taking which is 0.2 mg, because by this dosage we keep the serum TSH level slightly suppressed . In Iraq now there is no any specialized center for doing hypersensitivity test. Thanks for all, Dr. Muhamed Aydin, MD Iraq
RESPONSE- Urticaria is associated with Graves disease, but not to my knowledge with thyroid cancer. Possibly she has two unrelated diseases. Excess thyroid hormone can cause skin sensitivity, as happens in hyperthyroidism, and would possibly worsen urticaria. It is also possible, though unlikely, that she is allergic to the dye in the 100ug T4 tablet. Also, she may be cured of her thyroid tumor, especially if she had three valid scans with no evidence of disease (although we do not have data on TG).
Thus you might try giving her the 50ug tablets which have no dye in them. You also might cut down her T4 dose. It only takes a small increment above replacement to keep the TSH low, and in fact it is not clear that she needs to have her TSH suppressed, assuming she is really free of disease. Often steroids are needed for a time. If one antihistamine dose not work, one can try another-hydroxizine, cetirizine, and even cyproheptidine- and also try to eliminate allergenic contacts. Detergents, perfumes, jewelry, drugs, cosmetics, special foods, can be serially eliminated, but unfortunately often without benefit. In my experience after a time the problem subsides, but it is very difficult. I am not aware that there is a better or more specific set of answers.There is a recent review of this problem in IMMUNOL ALLERGY CLIN NORTH AMERICA, MAY 04, if you can somehow get a copy.Best regards,  L De Groot, MD

HURTHLE CELL CARCINOMA,  RESIDUAL DISEASE POST-OP

RESPONSE--I am unaware of any connection between such stomach complaints and Hashimoto's thyroiditis.  It is not clear whether the stomach pain comes on only at the time she has episodes of urticaria, which might then tie these 2 together (there is a known association of the latter with Hashimoto's - see below).  Another rare association is with serositis (but the patient has no evidence of peritoneal fluid as I see it) and there is, finally, an increase in H pylori in one study of autoimmune thyroid disease patients (J Clin Gastroenterol,1998,26,259) but again I am sure this has been excluded.  Has she had a biopsy at the time of an attack to see if there is any inflammation or oedema in the stomach wall?

Regarding the other questions I would only increase the thyroxine if the TSH suggests the need for it, but in this unusual case I would be tempted to keep the TSH as low as possible within the reference range, since the cause of the problem is obscure and therefore optimising thyroid replacement may have some inexplicable effect.  If the attacks are brief I cannot see that there will be an effect of TPO antibodies and finally I have never seen such a case, so don't know whether thyroid function tests would be indicated - having heard about this lady I guess I would do them! Prof Anthony Weetman

Response--This is an interesting patient with Hashimoto’s thyroiditis. At first I would like to know the reason why this patient had subtotal thyroidectomy. Do the episodes of severe stomach pain associate with the attacks of urticaria or angioedema?  Do the two occur at the same time?

1.       I am taking care of many patients with Hashimoto’s thyroiditis every day but I have never seen such a case. I don’t know any literatures on this problem.

2.       If the patient shows increased serum TSH , you should increase the amount of replacement dose but I don’t think that these episodes are related to the condition of hypothyroidism.

3.       There are several reports that there is association between urticaria and autoimmune thyroid diseases, either Hashimoto’s thyroiditis or Graves’ disease (Lanigan et al. Clin Exp Dermatol 12:335, 1987; Heymann J Am Acad Dermatol 40:229, 1999). Urticaria is induced by several mechanisms including allergy and autoimmunity. If urticaria and stomach pain occur at the same time, both may have intimate relation, but not relate to Hashimoto’s thyroiditis. I don’t know the tests to clarify this relationship.

4.       As you know, anti-thyroid antibodies are frequently found (around 10% ) in adult women and may not have direct effect on stomach

  Prof Nobu Amino

ABNORMAL THYROID TESTS IN PREGNANCY
QUESTION- Mrs. S is a 28 year old female with no significant past medical history, who is at 27 weeks gestation. Her pregnancy to date has been normal, some nausea during the first trimester, but she has put on an appropriate amount of weight and is tolerating foods well. Her thyroid function tests done are as follows:
8/17/04:
TSH: 0.046 (low )
T4: 9.9
T3 Uptake: 16.1( low)
Free thyroxine index: 1.6
8/24/04
TSH: 0.20 (0.34-5.60)
FT4: 0.50 (0.58-1.64)
FT3:2.6 (2.3-4.2)
8/26/04
TSH; 0.246 (0.350-5.500)
FT4: 0.88 (0.89-1.80)
FT3: 2.4 (2.3-4.2)
The patient has a normal thyroid on exam and no clinical features of hyper or hypothyroidism. Does she have secondary hypothyroidism? If so how do I work her up in pregnancy? Thank You,
Bindubalbalan@aol.com

RESPONSE-1 Typically the elevated hCG levels in early pregnancy can suppress the TSH modestly. Also, free T4 or T3 assays may perform erratically in the presence of high TBG, which your patient should have. Please check the total T4, and the TSH again. Total T4 should be elevated. Probably she is well, and the tests are a bit off for these reasons. Kind regards,
L De Groot,MD

RESPONSE 2
1) I do not really know whether this patient has 'central hypothyroidism' since this diagnosis was solely based on the absence of a rise in serum total T4 during pregnancy, with real data not provided , no measurement of free T4 done, and in addition normal serum cortisol (whatever this really means !).
2) In any case with hypothyroidism during a pregnancy (be it primary or supposedly secondary), I think that it is important to confirm the etiology of the condition before embarking on therapy : ultrasonography; thyroid antibodies; other pituitary hormone measurements; 24-hr urinary cortisol excretion; etc.
3) the absence of a rise in total T4 might have other potential explanations : iodine deficiency (unlikely in Goa probably) or congenital absence of TBG (hemizygote in the case of females) for instance.
4) if the patient has delivered now, it should be possible to re-evaluate the diagnosis of central hypothyroidism.
Prof Daniel GLINOER

PROGRESSIVE OPHTAHALMOPATHY IN AN ELDERLY MAN

QUESTION-I hope you will be able to provide information or direct me to 

literature on the following....my 82 year old father was diagnosed with 

Hashimoto Hypothyroidism 2 years ago. One year later, he developed significant 

thyroid associated ophthalmopathy including diplopia and proptosis (one eye 

worse then the other).  After 4 months of worsening symptoms, orbital X-ray was 

performed. Initially, follow-up exams indicated improvement. Now, 2 years after 

the initial diagnosis of Hashimoto Hypothyroidism, he has Graves Disease, and 

the eye that initially had minimal involvement now has significantly proptosis. 

My dad is being seen at Columbia Presbyterian for the Thyroid Associated 

Opthalmopathy, and his endocrinologist recently stopped the thyroid supplement 

as he has now gone from hypo to hyperthyroidism. One other worthy note - 

Myesthneia Gravis was ruled out 

>             The outstanding question I have is - how long does Thyroid Associated 

Opthalmopathy tend to last in seniors, and is thyroid related medical treatment 

different for someone in his age group?              Any information, or reference 

to literature on TAO in seniors would be greatly appreciated.   

           Thank You,Birdie D'Andrea,RN

RESPONSE-Dear Ms. D'Andrea,  

Thyroid-associated ophthalmopathy is most common in women in their 40s and 50s, 

and is fairly uncommon in elderly men. I know of no study concerning differences 

in the eye problems or responses to treatment in the elderly. However, in my 

experience and in that of others, there does seem to be more involvement of the 

eye muscles with diplopia in the elderly, while younger patients tend to have 

more enlargement of the fat tissues behind the eyes with proptosis and extensive 

inflammation. That said, clearly your father has a combination of both. I would 

recommend the same eye treatment for him as I would for a younger person. As the 

specifics would depend on the details of his eye exam and discussions with him, 

I can not tell you exactly what (if any) eye treatment I would recommend for him 

at present.The duration of eye problems varies considerably from patient to 

patient, ranges from about 6 months to several years' time, and does not seem to 

be related to the age of the patient. The type of treatment needed for his 

hyperthyroidism is also not directly age-dependant, but would depend on his 

general health status. It is particularly important in the elderly to maintain 

normal thyroid hormone levels as older individuals are especially prone to heart 

problems when hyperthyroid. Rebecca Bahn, MD

HYPOTHYROIDISM, DELAYED PUBERTY, MENTAL RETARDATION

QUESTION-Thank you very much for taking my questions.  I have recently seen a 15 yo boy 

with severe hypothyroidism (TSH 506 uIU/ml and total T4 of 1.05 ug/dl).  He also 

has significant short stature, being 4 feet 5 inches.  He is Tanner 2 and has a 

low testosterone of 64.  Unfortunately for him, his epiphysis are 90% closed by 

his bone age.  I am concerned that if I treat him with thyroid replacement 

alone, he is going to go through an accelerated puberty, and will not end up 

with an acceptable height.  So, we are contemplating starting him on a GnRH 

analog (leuprolide acetate) to shut down his puberty and supplement him with 

growth hormone at 0.37 mg/kg/week to improve his growth potential.  Since this 

requires a lot of work and a lot of financial resources, I was wondering if I 

could ask you a few questions...

1. What is the mechanism for pubertal delay in boys with severe hypothyroidism 

(ie why do we see precocious puberty in girls with severe primary 

hypothyroidism, but see the opposite in boys)?

2. Are there any other studies (other than the one that I attached) that treated 

peripubertal boys with bone age delay in hypothyroidism with a GnRH analog 

and/or growth hormone?  Do you think this is a reasonable approach?

3. This boy is also mildly retarded.  Are there any syndromes that have mental 

retardation, severe short stature, hypogonadotropic hypogonadism and primary 

hypothyroidism?  I thought of Laurence- Moon- Biedl syndrome, but this boy did 

not have polydactaly, he has no kidney or vision problems, so I think this 

particular diagnosis is unlikely for him.

I eagerly await your response.  Thanks so much!

 Alexandra L. Haagensen, MD, Children's Hospital Boston

RESPONSE-

#1.--Thyroid hormone is essential for bone growth, and, therefore, bone age advancement.  It appears that th CNS maturation that is necessary for puberty has the same determinants as those necessary for bone age maturation.; therefore, any disorder associated with delayed BA is associated with delayed puberty.  In both sexes.  The sex precocity seen in a tiny minority of hypothyroid children is poorly understood (see my chapter on female puberty in Sperling's textbook of pediatric endocrinology).

#2.--You can search PubMed as well as I for the latest.  But this is a standard approach.

CONGENITAL THYROID DEFICIENCY, NO RAIU, AND THYROID CANCER

ABNORMAL THYROID TESTS IN PREGNANCY

NORMAL THYROID TESTS EXCEPT FOR ELEVATED RT3

SURGERY WITH ADRENAL MASS ; “INCIDENTAL” MEDULLARY CARCINOMA

HYPOTHYROISIM, RENAL INSUFFICIENCY, AND RAI THERAPY

THYROTOXICOSIS AND PREGNANCY. 14 Jul 2004

“SUBCLINICAL HYPOTHYROIDISM” WITH NORMAL freeT4 AND TSH

THYROID CYST, AND MILD HYPERTHYROIDISM, IN PREGNANCY

THYROTOXIC HYPOKALEMIC PARALYSIS AND 131-I THERAPY

THYROTOXICOSIS, VENTRICULAR FIBRILLATION, HYPOKALEMIA

OPHTHALMOPATHY ONSET LONG AFTER THYROTOXICOSIS

"INCIDENTAL" MEDULLARY CARCINOMA

GROWING HOT NODULE

MALABSORPTION OF THYROXINE?

CENTRAL HYPOTHYROIDISM ?

NEONATE WITH LARGE GOITER

THYROID CARCINOMA DIAGNOSED BY BRONCHOSCOPY

SUBLINICAL HYPERTHYROIDISM AND SUBSTERNAL GOITER

NODULES, POSITIVE ANTIBODIES, AND TREATMENT?

AMIODARONE AND RECURRENT GRAVES’DISEASE

Therapy of a patient with a solitary vertebral metastasis

ATYPICAL GRAVES’ DISEASE

THYROIDITIS: RELATION TO SERTRALINE, AND LACK OF MELANIN

131-I TREATMENT IN RENAL FAILURE (13 May 03)

THYROXINE DOSAGE AND SURGERY, OR AFTER 131-I TREATMENT (10 May 03)

POSITIVE ANTIBODIES, AND GROWING NODULES (5 May 03)

THYROID HORMONE AND TSH LEVELS DURING PREGNANCY

Followup in differentiated thyroid cancers under 1cm

Hurthle cell nodule and Hyperthyroidism in Hashimoto’s gland(31Mar03)

HIVES, ANGIOEDEMA, AND HASHIMOTO'S THYROIDITIS

HYPERTHYROIDISM IN PREGNANCY?

HYPERTHYROIDISM IN PREGNANCY--CAUSE??, AND TREATMENT??

CONGENITAL THYROID DEFICIENCY, NO RAIU, AND THYROID CANCER

QUESTION- Thanks for taking the time to read this. I am a registrar from South Africa with an interesting young patient in whom your opinion would be greatly Appreciated. This young male first presented as a neonate with congenital hypothyroidism. At that time a thyroid uptake scan showed no thyroid tissue anywhere and a diagnosis of congenital thyroid agenesis was made. He was started on thyroxin, followed up for a while, and then was lost to follow up.

A few years later he returned to the clinic with a mass in the neck which clinically appeared to be a thyroid mass! Reviewing his initially uptake scans showed no uptake, and a repeat isotope scan again showed no uptake, however an ultrasound of his neck showed a multinodular thyroid gland. Too cut a long story short, he was found to have follicular Ca ofthe thyroid (most likely due to unsuppressed TSH) and a total thyroidectomy was performed. The diagnosis was then altered from thyroid agenesis, to an Iodine trapping defect or some form of dyshormonogenisis as uptake scan remained completely negative. He was treated with thyroxine post operatively and again absconded from follow up.

He is now 15yrs old. Of normal height and weight for his age, and has returned to our services with a lump in his neck. He is otherwise asymptomatic. A Fine needle aspiration of the lump (which is a lymph node in the cervical chain) shows follicular cells and the presumption is that the follicular Ca ( which on initial removal had extended through the thyroid capsule and invaded the vessels) has disseminated. A SPECT scan has shown uptake in a chain of lymph nodes in the neck extending into the thorax.

My question is: In lieu of his iodine trapping defect it will not be possible to treat this with Radio-active iodine, do you have any suggestions in management of this young man.

Kind regards,
Jonathan Mervis (paediatric registrar)

RESPONSE- This is a very interesting and intriguing case. I can try some comments.

1. Iodine trapping defect can cause hypothyroidism but is always associated with goiter. Thus this cannot be the cause of the patient's congenital hypothyroidism, unless in addition the patient had also an other genetic defect responsible for thyroid agenesis (such as absence of thyroid specific transcription factor TTF1,2 or others).
2. Whatever the reason for his thyroid agenesis, I guess that it was not a complete agenesis, but rather the patient might have some small thyroid tissue not visible in the scan. The follicular tumor may have developed from this remnant.
3. Another possibility to explain the lack of uptake (is this true also in the metastatic tissue? this is not clearly stated in your report) may be a defective TSH or a TSH-receptor. Measurement of serum Tg (and Tg immuno-staining in the tumor tissue) would also be interesting to know.
4. Regarding treatment, I think that I would try stimulation with recombinant human TSH (Thyrogen) to see whether it is possible to elicit iodine uptake and Tg production. A part from that I think that surgery is the only other option.

Thank you for giving me the opportunity to know about this case,
Furio Pacini, MD

ABNORMAL THYROID TESTS IN PREGNANCY

QUESTION- Mrs. S is a 28 year old female with no significant past medical history, who is at 27 weeks gestation. Her pregnancy to date has been normal, some nausea during the first trimester, but she has put on an appropriate amount of weight and is tolerating foods well. Her thyroid function tests done are as follows:

The patient has a normal thyroid on exam and no clinical features of hyper or hypothyroidism. Does she have secondary hypothyroidism? If so how do I work her up in pregnancy?

Thank You,
Bindubalbalan@aol.com

RESPONSE- Typically the elevated hCG levels in early pregnancy can suppress the TSH modestly. Also, free T4 or T3 assays may perfrom erratically in the presence of high TBG, which your patient should have. Please check the total T4, and the TSH again. Total T4 should be elevated. Probably she is well, and the tests are a bit off for these reasons.

Kind regards,
L De Groot,MD

NORMAL THYROID TESTS EXCEPT FOR ELEVATED RT3

QUESTION-I am a physician who practice in El Paso, TX. I just got a patient complaining of fatigue with the following thyroid panel results:

TSH - 2.04 uIU/mL
T4 Total - 8.55 ug/dL (4.87 - 11.72)
T Uptake - 43.3 % (32 - 51)
Free Tiroxine Index - 9.26 ug/dL (5.93 - 13.13)
T3 Total - 1.03 ng/ml (0.58 - 1.59)
T3 Free - 2.90 pg/ml (1.7 - 3.7)
T4 Free - 1.37 ng/dL (0.70 - 1.48)
Thyroglobulin Autoantibodies - 14 U/mL (Reference range <60)
Thyroid Peroxidase Autoantibodies - 19 U/mL (Reference range <60)
Reverse T3 - 741 pg/ml (90 - 350)

All of the above tests were within range except Reverse T3 (normal ranges-90 to 350 pg/mL). I also read in some articles that TSH levels above 2.0 could be a sign of hypothyroidism. Do you colleagues think that a T3 thyroid replacement will benefit my patient in his fatigue?. Also any idea of why he got high Reverse T3 values?. He is currently taking the following drugs:

Amytriptiline: 125mg daily
Pherpenazine: 4mg daily
Indera (propanolol): 20mg daily

As fas as depression, he is now very stable and no showing signs or symptoms of depression.

I would appreciate your feedback regarding this patient.

Thanks in advance,
Roberto Meza M.D., El Paso, TX

RESPONSE- The explanation of the situation is possibly as follows. Even to the more recent stringent criteria his TSH is normal as well. The increase in rT3 may be caused by the use of propranolol. I patch the abstract of a study that we did, below. It shows, see attachment, that in healthy subjects the effect of propranolol on parameters of serum T3 and serum T4 is moderate but huge on serum rT3. I assume that, because the dose of propranolol that your patient is using is low, only rT3 falls out of range, but not T3 and T4 parameters. However the situation is not completely comparable as our subjects were healthy young men treated for the purpose of the study with 200 micrgr. T4/day, and 3 times daily with 80 mgr propranolol. Furthermore the dose of propranolol that your patient is using is so low as compared to our subjects that I am surprised that rT3 is affected to such an extent. It may be that your patient also has a mild non-thyroidal illness where there is an early rise of rT3. Maybe, that a combination of these 2 factors explains the hormone profile of your patient. At any rate I am pretty sure that the thyroid function of your patient is normal and does not explains his complaints

Kind regards,
Georg Hennemann

Am J Physiol. 1988 Jul;255(1 Pt 1):Three-compartmental analysis of effects of D-propranolol on thyroid hormone kinetics. van der Heijden JT, Krenning EP, van Toor H, Hennemann G, Docter R.

Tracer thyroxine (T4), 3.3',5-triiodothyronine (T3), and 3,3',5'-triiodothyronine (rT3) kinetic studies were performed in normal T4 substituted subjects before and during oral D-propranolol treatment to determine whether changes in thyroid hormone metabolism in a propranolol-induced low-T3 syndrome result from inhibition of 5'-deiodination or inhibition of transport of iodothyronines into tissues. Data were analyzed according to a three-compartmental model of distribution and metabolism. T4 plasma appearance rate decreased by 16% (P less than 0.01), reflecting a decreased intestinal absorption of orally administered T4 during propranolol. Serum T4 and free T4 levels increased significantly by 14%, whereas T4 metabolic clearance rate (MCR) was lowered by 26% (P less than 0.001). No changes were observed in size of the three T4 compartments or in fractional and mass transfer rates of T4 from plasma to the rapidly (REP) and slowly (SEP) equilibrating pools. Serum T3, free T3, T3 plasma pool, T3 mass transfer rate to REP and SEP, and the T3 pool masses were all significantly decreased during propranolol to a similar extent as the T3 plasma production rate (PR). T3 MCR decreased by 14% (P less than 0.05). Serum total and free rT3 increased, whereas the rT3 MCR was substantially lowered during propranolol (P less than 0.001). The rT3 plasma pool, rT3 REP and SEP, and the mass transfer rates to REP and SEP increased, whereas no alterations were observed in rT3 PR and fractional transfer rates of rT3 to

SURGERY WITH ADRENAL MASS ; “INCIDENTAL” MEDULLARY CARCINOMA

Question
Thank you so much for responding to my e mails. I wish to get your views on these cases. 1) 43 year old male diagnosed with NHLymphoma 1991,post surgery,post RT.Incidental finding of 1.3 cm adrenal adenoma right, serial ct/mri of the adrenals showed increase in size 2003 1.8 cm,2004 1.6 cm. He is clinically ok, non hypertensive, the nodule looks silent and benign, HU <10. My questions are: a) he is to undergo a nasal surgery under general anesthesia, is it safe to proceed with surgery or do we have to r/o functioning adrenal nodule first? b) he also has subclinical hypothyroidism,ft4 11,tsh 12,anti tg>2000,anti tpo 130,thyroid scan, hyperfunctioning and warm nodules. Can his subhypo be attributed to the radiation he received while during treatment for HL ymphoma of the axillary node or is this definitely thyroiditis alone? can we also consider the thyroid nodules to be radiation exposure related? 2) female late 20s, 2002 presented with subclinical hypothyroidism and a discreet solid nodule on the right lobe.FNAC was colloid nodule. She received t4 suppression for about a year before finally deciding to have thyroidectomy. NO FROZEN section, surgery done at the suburb. Histopath showed medullary ca. Problem: surgery done was subtotal. Parathyroids were normal looking says the surgeon, patient non hypertensive .Should we subject patient to completion thyroidectomy, can we be guided by calcitonin level and cea alone at this time. 3) What exactly is the clinical significance of (histopath reading) HYPERPLASTIC nodules.We see a lot of these lately. Thanks so much sir for your time and wisdom.
Lynn F.W.Bilar,MD

Response

1. The adrenal mass seems to be a non functioning incidentaloma. The only test that I would recommend in view of a general anasthesia is measurement of plasma/urinary epinephrins just to exclude the rare possibility of pheocromocytoma. Regarding the thyroid, definitely the patient has autoimmune thyroiditis with subclinical hypothyroidism. This can develop spontaneously on a genetic background but that are also convincing evidence that autoimmune thyroiditis may be triggered by exposure to external radiation. Clinically it makes no difference, except that true cold nodules in the setting of radiation exposure have higher chance to be malignant and thus must be submitted to FNAC.
2. Medullary thyroid cancer is a potentially lethal disease and frequently presents with lymph node metastases, either clinically evident or unsuspected. In my opinion the patient should undergo a careful ultrasound of the neck for lymph nodes and calcitonin measurements before and after pentagastrin stimulation. If the results are fine, I would procede with completion thyroidectomy and dissection of the central node compartment. If there is suspicion of lateral lymph node involvement surgery should be more aggressive. In addition, being the patient young one should screen blood DNA for germline mutations of the ret proto-oncogene. This is because about 5-7% of apparently sporadic MTCs are indeed hereditary cases or "de novo" disease misdiagnosed as sporadic.
3. In my view hyperplastic nodule should refer to nodules as those found in the context of goiter where the disease is expression of minor TSH hyperstimulation, These leions are usually policlonal in origin as opposed to true adenomas which are usually monoclonal proliferations. I hope that this information answers your questions.

HYPOTHYROISIM, RENAL INSUFFICIENCY, AND RAI THERAPY

QUESTION
I am a physician with a 3.5 cm papillary thyroid cancer 5.5 weeks post total-thyroidectomy (no macroscopic extension, no known distant mets, but a few positive lymph nodes) about to undergo ablation with 150 mCi iodine next week. I was otherwise healthy, 43 years old, with no meds and no prior medical problems. Post operative calcium has been low 8.7 (reference 8.9-10.3), PTH - 48 (reference 14-72) - 48 hours off of calcium supplements. My concern is that my creatinine has crept up from 1.2 to 1.7 over the past two weeks as my TSH has risen above 65 - with BUN 5 to 8, C02 31 and otherwise normal electrolytes, normal albumin, total protein. I have read a few small series about renal insufficiency with profound hypothyroidism induced decreases in GFR [Kreisman SH. Arch Intern Med 1999; 159: 79-82]. A few related questions. What is your experience with this phenomenon - if any? Is it fully reversible? Is there anything I can do to ameliorate this decline and the potential for long term renal injury? Does my dose of radioactive iodine need to be cut due to renal insufficiency?
S Rothrock MD, Orlando, Florida

ANOTHER RESPONSE
The answers to your questions are a bit complicated You should also consult with a nephrologist to be sure there is no underlying renal disease.. However, my thoughts are as follows. Definitely severe hypothyroidism can reduce GFR and increase Cr, and this should be fully reversible. I am surprised that the BUN is so low, but perhaps this is also due to a decrease in diet and decreased metabolism . Generally a TSH above 30 is considered adequate for treatment. Severe hypothyroidism can be avoided by using the "Half dose protocol" , or recombinant TSH, as described in THYROIDMANAGER. There are wide variations in the dose chosen for ablation, with reasons for most choices. Your dose is on the "highish" side , I believe. The whole body radiation exposure will be increased by hypothyroidism and diminished GFR. Generally the whole body radiation is reasonably low in this proceedure, but can only be determined by knowing the dose administered, thyroid uptake, and retention time. It often is about 1/3 to 1/2 rad per mCi given, but this is only true if there is little RAIU in the thyroid. A nuclear medical person could give more accurate figures when RAIU is known. Renal insufficiency would increase whole body radiation to some extent, but its effect on treatment of the residual thyroid would not necessarily be in the same direction since retention of stable iodine might tend to decrease fractional RAIU. Your nuclear medical therapist is really in the best position to answer these questions, which involve several factors that are not available to me. In general keeping well hydrated would help reduce 131-I retention in the body, but perhaps this should also be done with caution, since there is a recent report of severe hyponatremia occurring in this situation. I hope these rather scattered comments are of use.
L De Groot,MD

THYROTOXICOSIS AND PREGNANCY. 14 Jul 2004

QUESTION
Dear Sir- What one would do with a 20 years old lady with a recently diagnosed graves disease who would like to get married next week. Her partner refused to delay the wedding and will not accept her to be on contraception. What would be the optimum management. Should we operate on her. Would it be better to do total or subtotal thyroidectomy. Is thyroid replacement therapy safe in pregnancy.
Dr Tarek Elatrozy, Gharbia, Egypt

RESPONSE
Thyroid replacement is certainly perfectly safe in pregancy. I hesitate to say what is optimum management, not knowing all about the patient. However it is common to carry patients thru pregnancy on antithyroid drugs, with caution not to overdose the antithyroid drug. If there is difficulty with medical management, it is also considered safe to prepare the patient with antithyroid drugs, and operate in the mid trimester. Usually the operation is a subtotal thyroidectomy, but some people prefer a more complete thyroidectomy if the surgeon is skilled and has a low risk of parathyroid or nerve damage in practice. Does this provide what you need?
L De Groot,MD

“SUBCLINICAL HYPOTHYROIDISM” WITH NORMAL freeT4 AND TSH

THYROID CYST, AND MILD HYPERTHYROIDISM, IN PREGNANCY